scholarly journals Extracellular Calcium-Dependent Modulation of Endothelium Relaxation in Rat Mesenteric Small Artery: The Role of Potassium Signaling

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Lise Hangaard ◽  
Peter B. Jessen ◽  
Dmitrii Kamaev ◽  
Christian Aalkjaer ◽  
Vladimir V. Matchkov
Keyword(s):  
Extracellular Calcium ◽  
Small Artery ◽  
Small Arteries ◽  
Calcium Dependent ◽  
Dependent Pathway

The nature of NO- and COX-independent endothelial hyperpolarization (EDH) is not fully understood but activation of small- and intermittent-conductance Ca2+-activated K+channels (SKCaandIKCa) is important. Previous studies have suggested that the significance ofIKCadepends onCa2+out. Also it has been suggested that K+is important through localizedK+outsignaling causing activation of the Na+,K+-ATPase and inward-rectifying K+channels (Kir). Here we tested the hypothesis that the modulating effect ofCa2+outon the EDH-like response depends onK+out. We addressed this possibility using isometric myography of rat mesenteric small arteries. WhenK+outwas 4.2 mM, relaxation to acetylcholine (ACh) was stronger at 2.5 mMCa2+outthan at 1 mMCa2+out. Inhibition ofIKCawith TRAM34 suppressed the relaxations but did not change the relation between the relaxations at the low and highCa2+out. ThisCa2+out-dependence disappeared at 5.9 mMK+outand in the presence of ouabain or BaCl2. Our results suggest thatIKCaare involved in the localizedK+outsignaling which acts through the Na+,K+-ATPase andKirchannels and that the significance of this endothelium-dependent pathway is modulated byCa2+out.

scholarly journals Calcineurin Activity Is Required for the Initiation of Skeletal Muscle Differentiation

2000 ◽  
Vol 149 (3) ◽  
pp. 657-666 ◽  
Author(s):  
Bret B. Friday ◽  
Valerie Horsley ◽  
Grace K. Pavlath
Keyword(s):  
Skeletal Muscle ◽  
Cell Fusion ◽  
Transcriptional Activation ◽  
Active Form ◽  
Extracellular Calcium ◽  
Molecular Signaling ◽  
Phenotypic Differentiation ◽  
Calcium Dependent ◽  
Sequence Of Events

Differentiation of skeletal muscle myoblasts follows an ordered sequence of events: commitment, cell cycle withdrawal, phenotypic differentiation, and finally cell fusion to form multinucleated myotubes. The molecular signaling pathways that regulate the progression are not well understood. Here we investigate the potential role of calcium and the calcium-dependent phosphatase calcineurin in myogenesis. Commitment, phenotypic differentiation, and cell fusion are identified as distinct calcium-regulated steps, based on the extracellular calcium concentration required for the expression of morphological and biochemical markers specific to each of these stages. Furthermore, differentiation is inhibited at the commitment stage by either treatment with the calcineurin inhibitor cyclosporine A (CSA) or expression of CAIN, a physiological inhibitor of calcineurin. Retroviral-mediated gene transfer of a constitutively active form of calcineurin is able to induce myogenesis only in the presence of extracellular calcium, suggesting that multiple calcium-dependent pathways are required for differentiation. The mechanism by which calcineurin initiates differentiation includes transcriptional activation of myogenin, but does not require the participation of NFAT. We conclude that commitment of skeletal muscle cells to differentiation is calcium and calcineurin-dependent, but NFAT-independent.

Modulation of Small Artery Function by Insulin in Young Women: Role of Adiposity

2020 ◽  
Vol 20 (8) ◽  
pp. 1244-1252
Author(s):  
Moulinath Banerjee ◽  
Linda Shaw ◽  
Valentyn Charlton-Menys ◽  
Phillip Pemberton ◽  
Rayaz Ahmed Malik ◽  
...  
Keyword(s):  
Endothelial Function ◽  
Young Women ◽  
Vascular Dysfunction ◽  
Direct Effects ◽  
Small Artery ◽  
Human Artery ◽  
Contractile Responses ◽  
Small Arteries ◽  
Before And After

Objectives: Vascular dysfunction is common in obesity. Insulin can directly modulate arterial function, but its role is unclear in obesity. We examined the influence of adiposity on direct effects of insulin on human artery responses. Methods: 22 healthy women were stratified by median BMI into lower (LA) (n=11) and higher adiposity (HA) (n=11). Small arteries from gluteal biopsies were tested for contractile responses to Noradrenaline (NA), the endothelium-dependent dilator Carbachol and the endothelium-independent dilator sodium nitroprusside were examined before and after incubation with 100 mU/ml human insulin. Results: Contractile responses were similar in the two groups. Insulin reduced NA-induced contraction in HA [3.5 (2.4-4.6) vs. 2.4 (1.4-3.4) mN/mm: p=0.004] but not those from LA [4.1 (2.8-5.3) vs. 3.7 (2.5-5.0) mN/mm: p=0.33]. Endothelium-dependent dilation (EDD) was significantly reduced in arteries from women in the HA (34.7 (18.8-50.6%)) compared to those from women in the LA (62.3 (46.2- 78.4); p=0.013). Insulin improved EDD (change in maximal dilation before/after insulin (%)) in arteries from the HA (37.7 (18.0 to 57.3) but not the LA (6.3 (-6.5 to 19.1), p=0.007. Conclusion: Reduced EDD evident in arteries from HA subjects improve by incubating in insulin. Hyperinsulinaemia may be necessary in maintaining endothelial function in obesity.

scholarly journals Role of extracellular calcium and calcium efflux in the activation of hepatic glycogenolysis by calcium-dependent hormones.

1985 ◽  
Vol 32 (2) ◽  
pp. 317-326 ◽  
Author(s):  
YOSHINOBU KOIDE ◽  
NOBUTAKA DEMURA ◽  
SATOSHI KIMURA ◽  
NOBUO KUGAI ◽  
KAMEJIRO YAMASHITA
Keyword(s):  
Extracellular Calcium ◽  
Calcium Efflux ◽  
Calcium Dependent

Effect of Annexins Translocated in Extracellular Vesicles on Tumorigenesis

2020 ◽  
Vol 20 ◽  
Author(s):  
Qionghui Wu ◽  
Haidong Wei ◽  
Wenbo Meng ◽  
Xiaodong Xie ◽  
Zhenchang Zhang ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Extracellular Vesicles ◽  
Immune Cell ◽  
Epithelial Mesenchymal Transition ◽  
Main Role ◽  
Tumor Cell Adhesion ◽  
Mesenchymal Transition ◽  
Calcium Dependent ◽  
Tumor Neovascularization

: Annexin, a calcium-dependent phospholipid binding protein, can affect tumor cell adhesion, proliferation, apoptosis, invasion and metastasis, as well as tumor neovascularization in different ways. Recent studies have shown that annexin exists not only as an intracellular protein in tumor cells, but also in different ways to be secret outside the cell as a “crosstalk” tool for tumor cells and tumor microenvironment, thus playing an important role in the development of tumors, such as participating in epithelial-mesenchymal transition, regulating immune cell behavior, promoting neovascularization and so on. The mechanism of annexin secretion in the form of extracellular vesicles and its specific role is still unclear. This paper summarizes the main role of annexin secreted into the extracellular space in the form of extracellular vesicles in tumorigenesis and drug resistance and analyzes its possible mechanism.

Oxidized LDLs Induce Massive Apoptosis of Cultured Human Endothelial Cells Through a Calcium-Dependent Pathway

1997 ◽  
Vol 17 (2) ◽  
pp. 331-339 ◽  
Author(s):  
Isabelle Escargueil-Blanc ◽  
Olivier Meilhac ◽  
Marie-Thérèse Pieraggi ◽  
Jean-François Arnal ◽  
Robert Salvayre ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Human Endothelial Cells ◽  
Calcium Dependent ◽  
Dependent Pathway ◽  
Massive Apoptosis

Activation of bovine oocytes by protein synthesis inhibitors: new findings on the role of MPF/MAPKs†

2021 ◽  
Author(s):  
Cecilia Valencia ◽  
Felipe Alonso Pérez ◽  
Carola Matus ◽  
Ricardo Felmer ◽  
María Elena Arias
Keyword(s):  
Protein Synthesis ◽  
Kinase Activity ◽  
Cyclin B1 ◽  
Protein Synthesis Inhibitors ◽  
Vitro Fertilization ◽  
New Findings ◽  
Bovine Oocytes ◽  
Dependent Pathway

Abstract The present study evaluated the mechanism by which protein synthesis inhibitors activate bovine oocytes. The aim was to analyze the dynamics of MPF and MAPKs. MII oocytes were activated with ionomycin (Io), ionomycin+anisomycin (ANY) and ionomycin+cycloheximide (CHX) and by in vitro fertilization (IVF). The expression of cyclin B1, p-CDK1, p-ERK1/2, p-JNK, and p-P38 were evaluated by immunodetection and the kinase activity of ERK1/2 was measured by enzyme assay. Evaluations at 1, 4, and 15 hours postactivation (hpa) showed that the expression of cyclin B1 was not modified by the treatments. ANY inactivated MPF by p-CDK1Thr14-Tyr15 at 4 hpa (P < 0.05), CHX increased pre-MPF (p-CDK1Thr161 and p-CDK1Thr14-Tyr15) at 1 hpa and IVF increased p-CDK1Thr14-Tyr15 at 17 hours postfertilization (hpf) (P < 0.05). ANY and CHX reduced the levels of p-ERK1/2 at 4 hpa (P < 0.05) and its activity at 4 and 1 hpa, respectively (P < 0.05). Meanwhile, IVF increased p-ERK1/2 at 6 hpf (P < 0.05); however, its kinase activity decreased at 6 hpf (P < 0.05). p-JNK in ANY, CHX, and IVF oocytes decreased at 4 hpa (P < 0.05). p-P38 was only observed at 1 hpa, with no differences between treatments. In conclusion, activation of bovine oocytes by ANY, CHX, and IVF inactivates MPF by CDK1-dependent specific phosphorylation without cyclin B1 degradation. ANY or CHX promoted this inactivation, which seemed to be more delayed in the physiological activation (IVF). Both inhibitors modulated MPF activity via an ERK1/2-independent pathway, whereas IVF activated the bovine oocytes via an ERK1/2-dependent pathway. Finally, ANY does not activate the JNK and P38 kinase pathways.

scholarly journals A CACNA1A variant associated with trigeminal neuralgia alters the gating of Cav2.1 channels

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Eder Gambeta ◽  
Maria A. Gandini ◽  
Ivana A. Souza ◽  
Laurent Ferron ◽  
Gerald W. Zamponi
Keyword(s):  
Trigeminal Neuralgia ◽  
Missense Mutation ◽  
Neurotransmitter Release ◽  
Trigeminal System ◽  
Wild Type ◽  
Calcium Dependent ◽  
Whole Cell Patch Clamp ◽  
C Terminus ◽  
Dependent Inactivation

AbstractA novel missense mutation in the CACNA1A gene that encodes the pore forming α1 subunit of the CaV2.1 voltage-gated calcium channel was identified in a patient with trigeminal neuralgia. This mutation leads to a substitution of proline 2455 by histidine (P2455H) in the distal C-terminus region of the channel. Due to the well characterized role of this channel in neurotransmitter release, our aim was to characterize the biophysical properties of the P2455H variant in heterologously expressed CaV2.1 channels. Whole-cell patch clamp recordings of wild type and mutant CaV2.1 channels expressed in tsA-201 cells reveal that the mutation mediates a depolarizing shift in the voltage-dependence of activation and inactivation. Moreover, the P2455H mutant strongly reduced calcium-dependent inactivation of the channel that is consistent with an overall gain of function. Hence, the P2455H CaV2.1 missense mutation alters the gating properties of the channel, suggesting that associated changes in CaV2.1-dependent synaptic communication in the trigeminal system may contribute to the development of trigeminal neuralgia.

Role of iPLA2 and store-operated channels in agonist-induced Ca2+ influx and constriction in cerebral, mesenteric, and carotid arteries

2008 ◽  
Vol 294 (3) ◽  
pp. H1183-H1187 ◽  
Author(s):  
Kristen M. Park ◽  
Mario Trucillo ◽  
Nicolas Serban ◽  
Richard A. Cohen ◽  
Victoria M. Bolotina
Keyword(s):  
Carotid Arteries ◽  
Cerebral Arteries ◽  
Present Evidence ◽  
Voltage Gated ◽  
Functional Inhibition ◽  
Intracellular Ca ◽  
Dependent Pathway ◽  
Secondary Activation

Store-operated channels (SOC) and store-operated Ca2+ entry are known to play a major role in agonist-induced constriction of smooth muscle cells (SMC) in conduit vessels. In microvessels the role of SOC remains uncertain, in as much as voltage-gated L-type Ca2+ (CaL2+) channels are thought to be fully responsible for agonist-induced Ca2+ influx and vasoconstriction. We present evidence that SOC and their activation via a Ca2+-independent phospholipase A2 (iPLA2)-mediated pathway play a crucial role in agonist-induced constriction of cerebral, mesenteric, and carotid arteries. Intracellular Ca2+ in SMC and intraluminal diameter were measured simultaneously in intact pressurized vessels in vitro. We demonstrated that 1) Ca2+ and contractile responses to phenylephrine (PE) in cerebral and carotid arteries were equally abolished by nimodipine (a CaL2+ inhibitor) and 2-aminoethyl diphenylborinate (an inhibitor of SOC), suggesting that SOC and CaL2+ channels may be involved in agonist-induced constriction of cerebral arteries, and 2) functional inhibition of iPLA2β totally inhibited PE-induced Ca2+ influx and constriction in cerebral, mesenteric, and carotid arteries, whereas K+-induced Ca2+ influx and vasoconstriction mediated by CaL2+ channels were not affected. Thus iPLA2-dependent activation of SOC is crucial for agonist-induced Ca2+ influx and vasoconstriction in cerebral, mesenteric, and carotid arteries. We propose that, on PE-induced depletion of Ca2+ stores, nonselective SOC are activated via an iPLA2-dependent pathway and may produce a depolarization of SMC, which could trigger a secondary activation of CaL2+ channels and lead to Ca2+ entry and vasoconstriction.

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